Research in Dr. Rasenick's lab concerns neurotransmitter response and responsiveness as mediated via G proteins. A unique feature of this research is the demonstration that elements of the cytoskeleton are capable of modifying neurotransmitter response (signal transduction). Further, it is suggested that neurotransmitters which ar not directly coupled to the adenylyl cyclase system might modify that enzyme by altering the interaction between tubulin (a cytoskeletal component) and G proteins on the synaptic membrane. Over the period covered by this award, the molecular facets of interaction between tubulin G proteins will be determined, and synthetic peptides will be made and used to block this interaction. Hopefully, such studies will describe the physiologic events resulting from the transfer of GTP from membrane tubulin to specific G proteins. Several planned collaborations involve using a photoaffinity GTP analog made in this laboratory (AAGTP) to explore unique signal-mediated activation of G proteins. Collaborations are also proposed to study structural aspects of tubulin-G protein interaction. These studies involve either chemical crosslinking or immunocytochemistry at the EM level. Finally, several collaborative studies are proposed to study tubulin-G protein interactions using molecular genetic techniques. Hopefully, a more thorough understanding of the contributions which elements of the cytoskeleton make to neuronal signal transduction will also elucidate certain mysteries of mental function and dysfunction.